期刊
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
卷 10, 期 3, 页码 467-473出版社
XIA & HE PUBLISHING INC
DOI: 10.14218/JCTH.2021.00090
关键词
Hepatitis B virus; Hepatitis B virus X protein; Microtubule; Microtubule-associated protein 1S
资金
- Research Fund of Beijing Institute of Hepatology [Y-2021-6]
- WBE Liver Fibrosis Foundation [WBE2021052]
- Capital Special Fund for Health Development [2020-1-2182]
- National Science and Technology Key Project of China [2017ZX10201201]
The study reveals that hepatitis B virus can manipulate microtubule-associated protein 1S (MAP1S) to facilitate its transport and release. Furthermore, HBV X protein induces the formation of stable microtubules to promote the release of the virus.
Background and Aims: Continuous release and transmission of hepatitis B virus (HBV) is one of the main factors leading to chronic hepatitis B (CHB) infection. However, the mechanism of HBV-host interaction for optimal viral transport is unclear. Hence, we aimed to explore how HBV manipulates microtubule-associated protein 1S (MAP1S) and microtubule (MT) to facilitate its transport and release. Methods: The expression of MAP1S or acetylated MT was investigated by immunofluorescence, RT-PCR, immunoblotting, and plasmid transfection. MAP1S overexpression or knockdown was performed by lentiviral infection or shRNA transfection, respectively. HBV DNA was quantified using q-PCR. Results: Significantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR (p<0.01) and immunoblotting (p<0.001). Notably, stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls. MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells. Further, transfection with the hepatitis B virus X protein (HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls (p<0.0001), whereas HBVX- mutant-encoding HBV proteins (surface antigen, core protein, and viral DNA polymerase) hardly affected its expression. Conclusions: These results demonstrate that HBx induces the formation of stable MTs to promote the release of HBV particles through upregulating MAP1S. Thus, our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation, and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.
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